Geraldine Nouailles,Romina Bischoff,Kerstin Linke,Alexander Taylor,Birgitt Gutbier,Peter Pennitz,Cengiz Goekeri,Sandra Kunder,Anne Voß,Theresa C Brömel,Olivia Kershaw,Miha Milek,Vadim Farztdinov,Michael Mülleder,Sabrina Weissmüller,Corina C Heinz,Mayken Visser,Fabian Bohlaender,Katharina Ahrens,Dieter Beule,Achim D Gruber,Martin Koenig,Martin Witzenrath
{"title":"Trimodulin Supports Antibacterial Defence and Restricts Inflammation in Preclinical Pneumonia Models.","authors":"Geraldine Nouailles,Romina Bischoff,Kerstin Linke,Alexander Taylor,Birgitt Gutbier,Peter Pennitz,Cengiz Goekeri,Sandra Kunder,Anne Voß,Theresa C Brömel,Olivia Kershaw,Miha Milek,Vadim Farztdinov,Michael Mülleder,Sabrina Weissmüller,Corina C Heinz,Mayken Visser,Fabian Bohlaender,Katharina Ahrens,Dieter Beule,Achim D Gruber,Martin Koenig,Martin Witzenrath","doi":"10.1183/13993003.00392-2025","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nSevere pneumonia (sCAP) remains a global health challenge with high mortality despite advances in antibiotic therapy and supportive care. Immunoglobulin (Ig) therapies, especially IgM-containing ones, have shown promise in enhancing host defence and reducing inflammation. The CIGMA trial highlighted trimodulin's potential to lower mortality of sCAP patients with high C-reactive protein and low IgM levels.\r\n\r\nMETHODS\r\nWe investigated the protective effects of trimodulin on clinical status, bacterial burden, lung integrity, and inflammatory responses in murine models of lung injury, including both ventilator-induced lung injury (VILI) and infection-induced models with non-sterile inflammation.\r\n\r\nFINDINGS\r\nIn mice, trimodulin significantly protected against lethal pneumococcal pneumonia by reducing bacterial burden and disease severity while preserving alveolar barrier integrity and limiting lung edema. The antibacterial action of trimodulin was mediated through opsonophagocytosis, and its anti-inflammatory effects operated independently of the latter. When combined with ampicillin, trimodulin exhibited enhanced suppression of inflammation.\r\n\r\nINTERPRETATION\r\nOur findings in preclinical pneumonia models suggest that trimodulin could be a promising therapy for sCAP patients. We provide evidence that trimodulin enhances host defence, reduces detrimental pulmonary inflammation and barrier dysfunction, and limits pulmonary edema, which may explain its beneficial effects observed in sCAP patients.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"24 1","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Respiratory Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/13993003.00392-2025","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
BACKGROUND
Severe pneumonia (sCAP) remains a global health challenge with high mortality despite advances in antibiotic therapy and supportive care. Immunoglobulin (Ig) therapies, especially IgM-containing ones, have shown promise in enhancing host defence and reducing inflammation. The CIGMA trial highlighted trimodulin's potential to lower mortality of sCAP patients with high C-reactive protein and low IgM levels.
METHODS
We investigated the protective effects of trimodulin on clinical status, bacterial burden, lung integrity, and inflammatory responses in murine models of lung injury, including both ventilator-induced lung injury (VILI) and infection-induced models with non-sterile inflammation.
FINDINGS
In mice, trimodulin significantly protected against lethal pneumococcal pneumonia by reducing bacterial burden and disease severity while preserving alveolar barrier integrity and limiting lung edema. The antibacterial action of trimodulin was mediated through opsonophagocytosis, and its anti-inflammatory effects operated independently of the latter. When combined with ampicillin, trimodulin exhibited enhanced suppression of inflammation.
INTERPRETATION
Our findings in preclinical pneumonia models suggest that trimodulin could be a promising therapy for sCAP patients. We provide evidence that trimodulin enhances host defence, reduces detrimental pulmonary inflammation and barrier dysfunction, and limits pulmonary edema, which may explain its beneficial effects observed in sCAP patients.
期刊介绍:
The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.